Acyl lactylates are represented by the general structure: R--CO--(OCH CH.sub.3 CO).sub.n --OH where R is a straight or branched alkyl or aryl group consisting of 3 to 20 carbons and n=1 to 10. Acyl lactylates have been used in the food industry as dough conditioners and softeners and as oil-in-water emulsifiers in nondairy compositions such as coffee whiteners and vegetable oil based whipped toppings. They have also been used as emulsifiers in analgesic stick compositions and in conjunction with other co-emulsifiers to produce an emulsion base for cosmetic or pharmaceutical compositions. Typically, acyl lactylates are commercially available as a salt form for use in cosmetic formulations. The salt form is not effective as a permeation enhancer.
Other uses of acyl lactylates include their use as antimicrobial or antibacterial agents, and as a protectant against hair loss or in topical compositions for inducing, maintaining, or increasing hair growth. In general, permeation enhancers that are not normally toxic at the concentrations employed in cosmetic or medical compositions may exhibit toxic effects at the higher concentrations required to produce adequate permeation enhancement. Accordingly, acyl lactylates have not been used as a permeation enhancer alone or in combination with other permeation enhancing agents in order to increase the permeability of a body surface or membrane to a drug or active agent to transdermally deliver the drug or agent to the systemic circulation of a patient.
U.S. Pat. No. 4,184,978, incorporated herein in its entirety by reference, describes stable oil-in-water emulsion systems for use in cosmetics, toiletries, and pharmaceuticals. Acyl lactylates are disclosed as suitable emulsifiers.
U.S. Pat. No. 4,301,820, incorporated herein in its entirety by reference, describes a composition comprising at least one fatty acid lactylate and/or glycolate as a humectant compound in permanent waving compositions.
U.S. Pat. No. 4,702,916, incorporated herein in its entirety by reference, describes the use of acyl lactylates as emulsifiers in analgesic gel stick compositions.
U.S. Pat. No. 5,124,354, incorporated herein in its entirety by reference, describes a special protein tyrosine kinase inhibitor and a cosmetically acceptable vehicle. Surface active agents, including acyl lactylates, are disclosed as penetration enhancers that improve delivery of the composition to its site of action in the immediate environment of the hair follicle close to the dermal papilla.
European Patent Application 0 573 253 incorporated herein in its entirety by reference describes an anti-bacterial cosmetic composition for topical application to the skin and/or hair comprising C.sub.6 -C.sub.12 acyl lactylate or a derivative thereof as an anti-bacterial substance. The composition is especially beneficial in the treatment of unwanted hair loss.
European Patent Application 0 572 271 incorporated herein in its entirety by reference describes the use of acyl lactylates as preservatives in topical cosmetic compositions for prevention of the growth of undesired microorganisms in the skin or hair.
The transdermal route of parenteral delivery of drugs provides many advantages, and transdermal systems for delivering a wide variety of drugs or other beneficial agents are described in U.S. Pat. Nos. 3,598,122; 3,598,123; 3,731,683; 3,797,494; 4,286,592; 4,314,557; 4,379,454; 4,435,180; 4,559,222; 4,568,343; 4,573,999; 4,588,580; 4,645,502; 4,704,282; 4,816,258; 4,849,226; 4,908,027; 4,943,435; and 5,004,610, for example, all of which are incorporated herein by reference. In many cases, drugs which would appear to be ideal candidates for transdermal delivery are found to have such low permeability through intact skin that they cannot be delivered in therapeutically effective amounts from reasonably sized devices.
In an effort to increase skin permeability so that drugs can be delivered in therapeutically effective amounts, it has been proposed to pretreat the skin with various chemicals or to concurrently deliver the drug in the presence of a permeation enhancer. Various materials have been suggested for this, as described in U.S. Pat. Nos. 3,472,931; 3,527,864; 3,896,238; 3,903,256; 3,952,099; 4,046,886; 4,130,643; 4,130,667; 4,299,826; 4,335,115; 4,343,798; 4,379,454; 4,405,616; 4,746,515; 4,788,062; 4,820,720; 4,863,738; 4,863,970; and 5,378,730; British Pat. No. 1,011,949; and Idson, "Percutaneous Absorption," J. Pharm. Sci. (1975) 64:901-924.
To be considered useful, a permeation enhancer should have the ability to enhance the permeability of the skin for at least one and preferably a significant number of drugs. More importantly, it should be able to enhance the skin permeability such that the drug delivery rate from a reasonably sized system (preferably 5-50 cm.sup.2) is at therapeutically effective levels. Additionally, the enhancer when applied to the skin surface, should be non-toxic, non-irritating on prolonged exposure and under occlusion, and non-sensitizing on repeated exposure. Preferably, it should be odorless and capable of delivering drugs without producing burning or tingling sensations.